tbuckley/cabot-search huggingface dataset:
Latent COPD: a proposed new term in the disease nomenclature
Authors: Athena Gogali, Konstantinos Kostikas
Journal: European Respiratory Journal (2023)

<b>The proposed term "latent COPD" includes individuals with preserved FEV<sub>1</sub>/FVC, structural and/or functional abnormalities, and no/minimal symptoms, representing an alternative term to "pre-COPD" that is also a more substantial target for future research</b>https://bit.ly/3Mz1KPx
Physical manoeuvres in patients with ARDS and low compliance: bedside approaches to detect lung hyperinflation and optimise mechanical ventilation
Authors: Emanuele Rezoagli, Luca Bastia, Laurent Brochard, Giacomo Bellani
Journal: European Respiratory Journal (2023)

<b>Chest wall compression may detect lung hyperinflation at the bedside in patients undergoing mechanical ventilation with ARDS and low compliance. This manoeuvre may optimise ventilator settings during mechanical ventilation.</b>https://bit.ly/43lz8PU
Artificial intelligence: do we really need it in pulmonary function interpretation?
Authors: Irene Steenbruggen, Meredith C. McCormack
Journal: European Respiratory Journal (2023)

<b>It is inevitable that we as healthcare professionals will have to incorporate AI techniques. The risk of becoming overly dependent on AI techniques is real and should be diminished by transparency and collaborative oversight of all who are involved.</b>https://bit.ly/423dWg7
A novel take on idiopathic pulmonary fibrosis disease progression: localised autoimmunity
Authors: Manali Mukherjee, Martin Kolb
Journal: European Respiratory Journal (2023)

It is well established that several of the interstitial lung diseases (ILDs) are driven by autoimmunity, such as rheumatoid arthritis-associated ILD and systemic sclerosis-associated ILD. These are therefore considered to be autoimmune diseases and frequently treated with immunosuppressive drugs. Idiopathic pulmonary fibrosis (IPF) is not viewed as an autoimmune disorder, but nevertheless, autoantibodies routinely studied in clinical practice are found in IPF and other types of idiopathic interstitial pneumonias. Serological autoreactivities, such as anti-cyclic citrullinated peptide antibody (anti-CCP), antinuclear antibody, rheumatoid factor (RF) and anti-neutrophil cytoplasmic antibody, have been reported in IPF [1] similar to patients with a connective tissue disease. Localised autoimmune responses in the lungs might contribute to disease progression in IPF <https://bit.ly/44c2D73>
The right ventricle tamed
Authors: Frances S. de Man, Anton Vonk Noordegraaf
Journal: European Respiratory Journal (2023)

<b>The study of Samaranayake and co-workers builds on the strong physiological and biological evidence that beneficial effects of beta-blockers can be obtained in PAH patients with a mild haemodynamic profile, similar to the effects in left heart failure</b>https://bit.ly/3Kn3RVi
Microneedle Patch Loaded with Exosomes Containing MicroRNA‐29b Prevents Cardiac Fibrosis after Myocardial Infarction (Adv. Healthcare Mater. 13/2023)
Authors: Jianping Yuan, Hong Yang, Chunxia Liu, Lianbo Shao, Haixin Zhang, Kunyan Lu, Jingjing Wang, Yuanyuan Wang, Qian Yu, Yanxia Zhang, Yunsheng Yu, Zhenya Shen
Journal: Advanced Healthcare Materials (2023)

Myocardial Infarction Treatment In article 2202959, Qian Yu, Yanxia Zhang, Yunsheng Yu, Zhenya Shen, and co-workers develop a microneedle patch for delivery of exosomes containing microRNA-29b mimics with antifibrotic activity to prevent excessive cardiac fibrosis after myocardial infarction. This design takes the specific advantages of the microneedle patch, the exosome, and microRNA together into one system, showing a promising potential for clinical applications to treat myocardial infarction.
Novel Ionizable Lipid Nanoparticles for SARS‐CoV‐2 Omicron mRNA Delivery (Adv. Healthcare Mater. 13/2023)
Authors: Jinrong Long, Changxiao Yu, Honglei Zhang, Yiming Cao, Ye Sang, Haitao Lu, Zhen Zhang, Xin Wang, Huanyu Wang, Gengshen Song, Jing Yang, Shengqi Wang
Journal: Advanced Healthcare Materials (2023)
How Crystallographic Orientation‐Induced Fibrinogen Conformation Affects Platelet Adhesion and Activation on TiO<sub>2</sub> (Adv. Healthcare Mater. 13/2023)
Authors: Maja Struczyńska, Izabela Firkowska‐Boden, Nathan Levandovsky, Reinhard Henschler, Nour Kassir, Klaus D. Jandt
Journal: Advanced Healthcare Materials (2023)

Crystal Surfaces Crystallographic orientation, and therefore the arrangement and coordination number of surface atoms, defines the surface energy and wettability, subsequently controlling the cellular response to blood-contacting biomaterials. Depending on the crystallographic orientation of TiO2 (rutile) surfaces, fibrinogen adsorbs typically in a trinodular and/or globular conformation, determining platelet adhesion and activation. Rutile surface crystallographic orientation may determine the risk of blood clotting. This work is highlighted in article 2202508 by Klaus D. Jandt and co-workers.
On the material dependency of peri-implant morphology and stability in healing bone
Authors: Stefan Bruns, Diana Krüger, Silvia Galli, D.C. Florian Wieland, Jörg U. Hammel, Felix Beckmann, Ann Wennerberg, Regine Willumeit-Römer, Berit Zeller-Plumhoff, Julian Moosmann
Journal: Bioactive Materials (2023)

The microstructural architecture of remodeled bone in the peri-implant region of screw implants plays a vital role in the distribution of strain energy and implant stability. We present a study in which screw implants made from titanium, polyetheretherketone and biodegradable magnesium-gadolinium alloys were implanted into rat tibia and subjected to a push-out test four, eight and twelve weeks after implantation. Screws were 4 mm in length and with an M2 thread. The loading experiment was accompanied by simultaneous three-dimensional imaging using synchrotron-radiation microcomputed tomography at 5 μm resolution. Bone deformation and strains were tracked by applying optical flow-based digital volume correlation to the recorded image sequences. Implant stabilities measured for screws of biodegradable alloys were comparable to pins whereas non-degradable biomaterials experienced additional mechanical stabilization. Peri-implant bone morphology and strain transfer from the loaded implant site depended heavily on the biomaterial utilized. Titanium implants stimulated rapid callus formation displaying a consistent monomodal strain profile whereas the bone volume fraction in the vicinity of magnesium-gadolinium alloys exhibited a minimum close to the interface of the implant and less ordered strain transfer. Correlations in our data suggest that implant stability benefits from disparate bone morphological properties depending on the biomaterial utilized. This leaves the choice of biomaterial as situational depending on local tissue properties.
Gender equity of authorship in pulmonary medicine over the past decade
Authors: F. Geng, Y. Ren, H. Hou, B. Dai, J.B. Scott, S.L. Strickland, S. Mehta, J. Li
Journal: Pulmonology (2023)

Gender disparity in authorship broadly persists in medical literature, little is known about female authorship within pulmonary medicine. A bibliometric analysis of publications from 2012 to 2021 in 12 journals with the highest impact in pulmonary medicine was conducted. Only original research and review articles were included. Names of the first and last authors were extracted and their genders were identified using the Gender-API web. Female authorship was described by overall distribution and distribution by country/region/continent and journal. We compared the article citations by gender combinations, evaluated the trend in female authorship, and forecasted when parity for first and last authorship would be reached. We also conducted a systematic review of female authorship in clinical medicine. 14,875 articles were included, and the overall percentage of female first authors was higher than last authors (37.0% vs 22.2%, p<0.001). Asia had the lowest percentage of female first (27.6%) and last (15.2%) authors. The percentages of female first and last authors increased slightly over time, except for a rapid increase in the COVID-19 pandemic periods. Parity was predicted in 2046 for the first authors and 2059 for the last authors. Articles with male authors were cited more than articles with female authors. However, male-male collaborations significantly decreased, whereas female-female collaborations significantly increased. Despite the slow improvement in female authorship over the past decade, there is still a substantial gender disparity in female first and last authorship in high-impact medical journals in pulmonary medicine.
Effectiveness of JYNNEOS Vaccine Against Diagnosed Mpox Infection — New York, 2022
Authors: Eli S. Rosenberg, Vajeera Dorabawila, Rachel Hart-Malloy, Bridget J. Anderson, Wilson Miranda, Travis O’Donnell, Charles J. Gonzalez, Meaghan Abrego, Charlotte DelBarba, Cori J. Tice, Claire McGarry, Ethan C. Mitchell, Michele Boulais, Bryon Backenson, Michael Kharfen, James McDonald, Ursula E. Bauer
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

In 2022, an international Monkeypox virus outbreak, characterized by transmission primarily through sexual contact among gay, bisexual, and other men who have sex with men (MSM), resulted in 375 monkeypox (mpox) cases in the state of New York outside of New York City (NYC).*,† The JYNNEOS vaccine (Modified Vaccinia Ankara vaccine, Bavarian Nordic), licensed by the U.S. Food and Drug Administration (FDA) against mpox as a 2-dose series, with doses administered 4 weeks apart,§ was deployed in a national vaccination campaign.¶ Before this outbreak, evidence to support vaccine effectiveness (VE) against mpox was based on human immunologic and animal challenge studies (1-3). New York State Department of Health (NYSDOH) conducted a case-control study to estimate JYNNEOS VE against diagnosed mpox in New York residents outside of NYC, using data from systematic surveillance reporting. A case-patient was defined as a man aged ≥18 years who received a diagnosis of mpox during July 24-October 31, 2022. Contemporaneous control patients were men aged ≥18 years with diagnosed rectal gonorrhea or primary syphilis and a history of male-to-male sexual contact, without mpox. Case-patients and control patients were matched to records in state immunization systems. JYNNEOS VE was estimated as 1 - odds ratio (OR) x 100, and JYNNEOS vaccination status (vaccinated versus unvaccinated) at the time of diagnosis was compared, using conditional logistic regression models that adjusted for week of diagnosis, region, patient age, and patient race and ethnicity. Among 252 eligible mpox case-patients and 255 control patients, the adjusted VE of 1 dose (received ≥14 days earlier) or 2 doses combined was 75.7% (95% CI = 48.5%-88.5%); the VE for 1 dose was 68.1% (95% CI = 24.9%-86.5%) and for 2 doses was 88.5% (95% CI = 44.1%-97.6%). These findings support recommended 2-dose JYNNEOS vaccination consistent with CDC and NYSDOH guidance.
Statistical perspectives on using hepatocellular carcinoma risk models to inform surveillance decisions
Authors: Hamish Innes, Pierre Nahon
Journal: Journal of Hepatology (2023)

More than 50,000 people are diagnosed with hepatocellular carcinoma (HCC) every year in Europe. Many cases are known to specialist liver centres years before they present with HCC. Despite this, HCC is usually detected at a late stage, when prognosis is very poor. For more than two decades, clinical guidelines have recommended uniform surveillance for all patients with cirrhosis. However, studies continue to show that this broad-based approach is inefficient and poorly implemented in practice. A "personalised" approach, where the surveillance regimen is customised to the needs of the patient, is gaining growing support in the clinical community. The cornerstone of personalised surveillance is the HCC risk model - a mathematical equation predicting a patient's individualised probability of developing HCC within a specific time window. However, although numerous risk models have now been published, few are being used in routine care to inform HCC surveillance decisions. In this article, we discuss methodological issues stymieing the use of HCC risk models in routine practice - highlighting biases, evidence gaps and misconceptions that future research must address.
Gaussian Processes for real-time 3D motion and uncertainty estimation during MR-guided radiotherapy
Authors: Niek R.F. Huttinga, Tom Bruijnen, Cornelis A.T. van den Berg, Alessandro Sbrizzi
Journal: Medical Image Analysis (2023)

Respiratory motion during radiotherapy causes uncertainty in the tumor's location, which is typically addressed by an increased radiation area and a decreased dose. As a result, the treatments' efficacy is reduced. The recently proposed hybrid MR-linac scanner holds the promise to efficiently deal with such respiratory motion through real-time adaptive MR-guided radiotherapy (MRgRT). For MRgRT, motion-fields should be estimated from MR-data and the radiotherapy plan should be adapted in real-time according to the estimated motion-fields. All of this should be performed with a total latency of maximally 200 ms, including data acquisition and reconstruction. A measure of confidence in such estimated motion-fields is highly desirable, for instance to ensure the patient's safety in case of unexpected and undesirable motion. In this work, we propose a framework based on Gaussian Processes to infer 3D motion-fields and uncertainty maps in real-time from only three readouts of MR-data. We demonstrated an inference frame rate up to 69 Hz including data acquisition and reconstruction, thereby exploiting the limited amount of required MR-data. Additionally, we designed a rejection criterion based on the motion-field uncertainty maps to demonstrate the framework's potential for quality assurance. The framework was validated in silico and in vivo on healthy volunteer data (n=5) acquired using an MR-linac, thereby taking into account different breathing patterns and controlled bulk motion. Results indicate end-point-errors with a 75th percentile below 1 mm in silico, and a correct detection of erroneous motion estimates with the rejection criterion. Altogether, the results show the potential of the framework for application in real-time MR-guided radiotherapy with an MR-linac.
Digital twins: dynamic model-data fusion for ecology
Authors: Koen de Koning, Jeroen Broekhuijsen, Ingolf Kühn, Otso Ovaskainen, Franziska Taubert, Dag Endresen, Dmitry Schigel, Volker Grimm
Journal: Trends in Ecology & Evolution (2023)

Digital twins (DTs) are an emerging phenomenon in the public and private sectors as a new tool to monitor and understand systems and processes. DTs have the potential to change the status quo in ecology as part of its digital transformation. However, it is important to avoid misguided developments by managing expectations about DTs. We stress that DTs are not just big models of everything, containing big data and machine learning. Rather, the strength of DTs is in combining data, models, and domain knowledge, and their continuous alignment with the real world. We suggest that researchers and stakeholders exercise caution in DT development, keeping in mind that many of the strengths and challenges of computational modelling in ecology also apply to DTs.
Disentangling brain vasculature in neurogenesis and neurodegeneration using single-cell transcriptomics
Authors: Elizabeth E. Crouch, Tara Joseph, Elise Marsan, Eric J. Huang
Journal: Trends in Neurosciences (2023)

The vasculature is increasingly recognized to impact brain function in health and disease across the life span. During embryonic brain development, angiogenesis and neurogenesis are tightly coupled, coordinating the proliferation, differentiation, and migration of neural and glial progenitors. In the adult brain, neurovascular interactions continue to play essential roles in maintaining brain function and homeostasis. This review focuses on recent advances that leverage single-cell transcriptomics of vascular cells to uncover their subtypes, their organization and zonation in the embryonic and adult brain, and how dysfunction in neurovascular and gliovascular interactions contributes to the pathogenesis of neurodegenerative diseases. Finally, we highlight key challenges for future research in neurovascular biology.
Management of Lymph Node–positive Penile Cancer: A Systematic Review
Authors: Ashwin Sachdeva, Luke McGuinness, Łukasz Zapala, Isabella Greco, Herney Andres Garcia-Perdomo, Mithun Kailavasan, Tiago Antunes-Lopes, Benjamin Ayres, Lenka Barreto, Riccardo Campi, Juanita Crook, Peter Johnstone, Vivek Kumar, Kenneth Manzie, Jack David Marcus, Andrea Necchi, Pedro Oliveira, John Osborne, Lance C. Pagliaro, Chris Protzel, R. Bryan Rumble, Diego F. Sánchez Martínez, Philippe E. Spiess, Scott T. Tagawa, Michiel S. van der Heijden, Arie S. Parnham, Curtis A. Pettaway, Maarten Albersen, Vijay K. Sangar, Oscar R. Brouwer, Vasileios I. Sakalis
Journal: European Urology (2023)

Lymph node (LN) involvement in penile cancer is associated with poor survival. Early diagnosis and management significantly impact survival, with multimodal treatment approaches often considered in advanced disease. To assess the clinical effectiveness of treatment options available for the management of inguinal and pelvic lymphadenopathy in men with penile cancer. EMBASE, MEDLINE, the Cochrane Database of Systematic Reviews, and other databases were searched from 1990 to July 2022. Randomised controlled trials (RCTs), nonrandomised comparative studies (NRCSs), and case series (CSs) were included. We identified 107 studies, involving 9582 patients from two RCTs, 28 NRCSs, and 77 CSs. The quality of evidence is considered poor. Surgery is the mainstay of LN disease management, with early inguinal LN dissection (ILND) associated with better outcomes. Videoendoscopic ILND may offer comparable survival outcomes to open ILND with lower wound-related morbidity. Ipsilateral pelvic LN dissection (PLND) in N2–3 cases improves overall survival in comparison to no pelvic surgery. Neoadjuvant chemotherapy in N2–3 disease showed a pathological complete response rate of 13% and an objective response rate of 51%. Adjuvant radiotherapy may benefit pN2–3 but not pN1 disease. Adjuvant chemoradiotherapy may provide a small survival benefit in N3 disease. Adjuvant radiotherapy and chemotherapy improve outcomes after PLND for pelvic LN metastases. Early LND improves survival in nodal disease in penile cancer. Multimodal treatments may provide additional benefit in pN2–3 cases; however, data are limited. Therefore, individualised management of patients with nodal disease should be discussed in a multidisciplinary team setting. Spread of penile cancer to the lymph nodes is best managed with surgery, which improves survival and has curative potential. Supplementary treatment, including the use of chemotherapy and/or radiotherapy, may further improve survival in advanced disease. Patients with penile cancer with lymph node involvement should be treated by a multidisciplinary team.
Improving non-small-cell lung cancer survival through molecular characterization: Perspective of a multidisciplinary expert panel
Authors: M.G.O. Fernandes, A.S. Vilariça, B. Fernandes, C. Camacho, C. Saraiva, F. Estevinho, H. Novais e Bastos, J.M. Lopes, P. Fidalgo, P. Garrido, S. Alves, S. Silva, T. Sequeira, F. Barata
Journal: Pulmonology (2023)
Immune Checkpoint Inhibitors and the Exposome: Host-Extrinsic Factors Determine Response, Survival, and Toxicity
Authors: Elio Gregory Pizzutilo, Rebecca Romanò, Laura Roazzi, Alberto G. Agostara, Sara Oresti, Annalisa Zeppellini, Laura Giannetta, Giulio Cerea, Diego Signorelli, Salvatore Siena, Andrea Sartore-Bianchi
Journal: Cancer Research (2023)

Cancer immunotherapy, largely represented by immune checkpoint inhibitors (ICI), has led to substantial changes in preclinical cancer research and clinical oncology practice over the past decade. However, the efficacy and toxicity profiles of ICIs remain highly variable among patients, with only a fraction achieving a significant benefit. New combination therapeutic strategies are being investigated, and the search for novel predictive biomarkers is ongoing, mainly focusing on tumor- and host-intrinsic components. Less attention has been directed to all the external, potentially modifiable factors that compose the exposome, including diet and lifestyle, infections, vaccinations, and concomitant medications, that could affect the immune system response and its activity against cancer cells. We hereby provide a review of the available clinical evidence elucidating the impact of host-extrinsic factors on ICI response and toxicity.
Proteasome Inhibition Sensitizes Liposarcoma to MDM2 Inhibition with Nutlin-3 by Activating the ATF4/CHOP Stress Response Pathway
Authors: Michael P. Ludwig, Matthew D. Galbraith, Neetha Paul Eduthan, Amanda A. Hill, Michael R. Clay, Cristiam Moreno Tellez, Breelyn A. Wilky, Anthony Elias, Joaquin M. Espinosa, Kelly D. Sullivan
Journal: Cancer Research (2023)

Abstract Liposarcoma is the most commonly occurring soft-tissue sarcoma and is frequently characterized by amplification of chromosome region 12q13–15 harboring the oncogenes MDM2 and CDK4. This unique genetic profile makes liposarcoma an attractive candidate for targeted therapeutics. While CDK4/6 inhibitors are currently employed for treatment of several cancers, MDM2 inhibitors have yet to attain clinical approval. Here, we report the molecular characterization of the response of liposarcoma to the MDM2 inhibitor nutlin-3. Treatment with nutlin-3 led to upregulation of two nodes of the proteostasis network: the ribosome and the proteasome. CRISPR/Cas9 was used to perform a genome-wide loss of function screen that identified PSMD9, which encodes a proteasome subunit, as a regulator of response to nutlin-3. Accordingly, pharmacologic studies with a panel of proteasome inhibitors revealed strong combinatorial induction of apoptosis with nutlin-3. Mechanistic studies identified activation of the ATF4/CHOP stress response axis as a potential node of interaction between nutlin-3 and the proteasome inhibitor carfilzomib. CRISPR/Cas9 gene editing experiments confirmed that ATF4, CHOP, and the BH3-only protein, NOXA, are all required for nutlin-3 and carfilzomib-induced apoptosis. Furthermore, activation of the unfolded protein response using tunicamycin and thapsigargin was sufficient to activate the ATF4/CHOP stress response axis and sensitize to nutlin-3. Finally, cell line and patient-derived xenograft models demonstrated combinatorial effects of treatment with idasanutlin and carfilzomib on liposarcoma growth in vivo. Together, these data indicate that targeting of the proteasome could improve the efficacy of MDM2 inhibitors in liposarcoma. Significance: Targeting the proteasome in combination with MDM2 inhibition activates the ATF4/CHOP stress response axis to induce apoptosis in liposarcoma, providing a potential therapeutic approach for the most common soft-tissue sarcoma.